To the Editor:
Lung cancer screening (LCS) with low-dose computed chest tomography (CT) is a preventive service that has been recommended since 2013. The NLST (National Lung Screening Trial), a randomized controlled trial, demonstrated a relative reduction in overall and lung cancer mortality (1), and left discretion to manage incidental findings (7.5% of exams) to each site. A subsequent analysis did not show a difference in spending attributable to incidental findings (2), whereas a real-world study of incidental findings estimated that half of screening reimbursements were due to evaluation of incidental findings (3). Higher rates of incidental findings on chest CT are well known, with estimates ranging from 24% in diagnostic CT (4, 5) to 86% (6) and 94% (3) in screening CT. In NELSON (Dutch-Belgium Lung Cancer Screening Trial), incidental findings were determined to be mostly without clinical implication (7). Whether reporting incidental findings alters the risk/benefit ratio or the cost-effectiveness of LCS is unknown.
The objective of this study was to determine whether reported rates of incidental findings in a large decentralized LCS program are higher in a university imaging center.
Methods
Study population
With the approval of the University of Minnesota Institutional Review Board, demographic characteristics and CT results were extracted from the Lung Cancer Screening Registry. LCS exams that had performed since inception of the program (December 12, 2013 to January 31, 2018; n = 2,227) were reviewed. Twenty-eight exams (1%) were excluded from analysis due to duplicate entry, incomplete records, or never-smoker status. Informed consent and authorization under the Health Insurance Portability and Accountability Act of 1996 were waived for this retrospective study.
The University of Minnesota Health is located in a large metropolitan area (8) and is affiliated with a health system encompassing five hospitals and over 40 clinics with a shared electronic health record. Affiliated imaging centers contract interpretation to a community radiology practice, whereas University Imaging Center exams are interpreted by radiology residents and faculty. Image acquisition and structured reports are standardized in accordance with the American College of Radiology (Lung Imaging Reporting and Data System [Lung-RADS]) (9).
Statistical Analyses
Demographic and exam characteristics were reported at the patient level (Table 1) and exam level (Table 2) using descriptive statistics. A multivariable general estimating equations model was used to test the hypothesis that incidental findings are more commonly reported in university imaging centers. The general estimating equations model, which uses exam-level data, accounts for within-subject correlation of repeated exams and adjusts for clinical factors such as age, sex, race (white vs. other), pack-years, smoking status (current vs. former), Lung-RADs category, insurance type, and time from the earliest exam date in the cohort. Coefficients and 95% confidence intervals were exponentiated to obtain the odds ratio estimates. Analyses were completed using R Version 3.4 and SAS Version 9.4 (SAS Institute Inc.). P values less than 0.05 were considered statistically significant.
Table 1.
Demographics and exam characteristics of 1,715 patients who underwent lung cancer screening by low-dose computed tomography between December 2013 and January 2018
| Overall N (Column %) | LDCT Imaging Site N (Column %) |
|||
|---|---|---|---|---|
| University | Community Partner | Both | ||
| Number of patients | 1,715 (100) | 644 (100) | 1,013 (100) | 58 (100) |
| Eligible by USPSTF pack-year and age criteria at first exam* | 1,490 (86.9) | 550 (85.4) | 889 (87.8) | 51 (87.9) |
| Age at first scan, years (median, range) | 63 (36–81) | 62 (36–80) | 64 (44–81) | 62 (53–78) |
| Sex | ||||
| Female | 919 (53.6) | 338 (52.5) | 549 (54.2) | 32 (55.2) |
| Male | 796 (46.4) | 306 (47.5) | 464 (45.8) | 26 (44.8) |
| Race | ||||
| American Indian or Alaska native | 10 (0.6) | 7 (1.1) | 3 (0.3) | 0 (0) |
| Asian | 14 (0.8) | 3 (0.5) | 11 (1.1) | 0 (0) |
| Black or African American | 63 (3.7) | 38 (5.9) | 23 (2.3) | 2 (3.5) |
| Native Hawaiian or other Pacific Islander | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| White | 1,521 (88.7) | 524 (81.4) | 943 (93.1) | 54 (92.1) |
| Refused/unknown | 107 (6.2) | 72 (11.2) | 33 (3.3) | 2 (3.5) |
| Number of LCS LDCT exams received during the study period | ||||
| One | 1,317 (76.8) | 506 (78.6) | 811 (80.1) | 0 (0) |
| Two or more | 398 (23.2) | 138 (21.4) | 202 (19.9) | 58 (100) |
| Incidental finding | ||||
| Reported | 752 (43.7) | 430 (66.8) | 285 (28.1) | 37 (63.8) |
| Not reported | 963 (56.2) | 214 (33.2) | 728 (71.9) | 21 (36.2) |
| Smoking status at time of screening | ||||
| Former smoker | 668 (39.0) | 254 (39.4) | 394 (38.9) | 20 (34.5) |
| Current smoker | 1,005 (58.6) | 369 (57.3) | 603 (59.5) | 33 (56.9) |
| Varied between scans | 42 (2.5) | 21 (3.5) | 16 (1.6) | 5 (8.6) |
| Insurance coverage at time of screening | ||||
| Medicaid | 263 (15.3) | 133 (20.6) | 116 (11.5) | 14 (24.1) |
| Medicare | 837 (48.8) | 295 (45.7) | 514 (50.8) | 28 (48.3) |
| Private insurance | 1,159 (67.6) | 406 (62.8) | 708 (70.0) | 46 (79.3) |
| Self-pay | 14 (0.8) | 5 (0.8) | 6 (0.6) | 3 (5.2) |
| Unknown | 21 (1.2) | 16 (2.5) | 4 (0.4) | 1 (1.7) |
| More than one type | 568 (33.1) | 204 (31.6) | 333 (32.9) | 31 (53.4) |
| Varied between scans | 77 (4.5) | 20 (3.1) | 39 (3.9) | 18 (31.0) |
| Pack-year history at first scan (median, range) | 40.0 (1–260) | 40.0 (2–260) | 40.0 (1–218) | 40.5 (10–120) |
| Lung-RADS | ||||
| 1 | 340 (19.8) | 61 (9.5) | 276 (27.3) | 3 (5.2) |
| 2 | 933 (54.4) | 411 (63.8) | 493 (48.7) | 29 (50.0) |
| 3 | 184 (10.7) | 63 (9.8) | 120 (11.9) | 1 (1.7) |
| 4a, 4b, or 4x | 123 (7.1) | 64 (9.9) | 59 (5.8) | 0 (0) |
| Varied between scans | 135 (7.7) | 45 (7.0) | 65 (6.4) | 25 (43.1) |
Definition of abbreviations: LCS = lung cancer screening; LDCT = low-dose computed tomography; Lung-RADS = Lung Imaging Reporting and Data System; USPSTF = United States Preventive Services Task Force.
Ninety-five percent of the participants did meet National Comprehensive Cancer Network Group 2 Lung Cancer Screening Eligibility: at least 50 years of age, at least 20 pack-years smoking history and additional risk factor.
Table 2.
Prevalence of incidental findings on 2,199 lung cancer screening exams between December 2013 and January 2018
| N (Column %) | Imaging Site |
||
|---|---|---|---|
| University N (Column %) | Community Partner N (Column %) | ||
| Number of exams | 2,199 (100) | 886 | 1,313 |
| Number of exams with incidental finding | 874 (39.8) | 540 (60.9) | 334 (25.4) |
| One incidental finding reported | 583 (26.5) | 308 (34.7) | 275 (20.9) |
| Two or more incidental findings reported | 291 (13.2) | 232 (26.2) | 59 (4.5) |
| Aortic aneurysm | 41 (1.9) | 24 (2.7) | 17 (1.3) |
| Coronary artery calcification | 481 (21.9) | 256 (28.9) | 225 (17.1) |
| Mass | 91 (4.1) | 50 (5.6) | 41 (3.1) |
| Adrenal | 17 (0.8) | 10 (1.1) | 7 (0.5) |
| Kidney | 18 (0.8) | 9 (1.0) | 9 (0.7) |
| Liver | 24 (1.1) | 9 (1.0) | 15 (1.1) |
| Thyroid | 16 (0.7) | 10 (1.1) | 6 (0.5) |
| Pancreas | 5 (0.2) | 3 (0.3) | 2 (0.2) |
| Breast | 5 (0.2) | 5 (0.5) | 0 (0) |
| Other | 6 (0.3) | 4 (0.5) | 2 (0.2) |
| Incidental lung finding | 262 (11.9) | 228 (25.7) | 34 (2.6) |
| Lymphadenopathy | 18 (0.8) | 10 (1.1) | 8 (0.6) |
| Other clinically significant abnormality | 111 (5.0) | 76 (8.6) | 35 (2.7) |
Results
A total of 1,715 patients underwent 2,199 CT exams during the study period. Most patients were current smokers and white individuals (Table 1). Incidental findings were reported in 44% of patients (n = 752) and 40% (n = 874) of exams. Patients with multiple exams (n = 398) had variable reporting over time of incidental findings. For example, coronary artery calcification was reported on the initial exam but not on subsequent exams in 30% of patients who had multiple exams (n = 138).
Incidental findings were reported in 67% of patients imaged exclusively at a university imaging center (n = 430), compared with 28% (n = 285) at a community imaging center and 64% (n = 37) for patients imaged at both. After adjusting for the effects of potential confounders, exams at university imaging centers were more likely to have an incidental finding reported compared with exams at community imaging centers (odds ratio, 5.4; 95% confidence interval, 4.4–6.5). The most common incidental findings were coronary artery calcification (20%) and incidental lung abnormalities (12%) (Table 2).
Discussion
This retrospective review of a large, decentralized LCS program demonstrated a higher rate of incidental findings than was reported in the NLST but was consistent with analyses of some NLST centers (10) and other LCS programs (3). Specifically, coronary artery calcification and incidental lung abnormalities were quite common. Current smokers, men, and individuals imaged at university imaging centers were more likely to have reported incidental findings. These results highlight the need to standardize reporting of LCS incidental findings.
The clinical importance of incidental findings varies. Coronary artery calcification severity reporting is recommended and corresponds to cardiac risk, which will impact prevention and treatment strategies (11). Our estimates of incidental lung abnormalities are similar to previous estimates (12), but the clinical benefit of reporting incidental lung abnormalities remains unclear. Future studies need to address clinician responses to incidental findings, costs associated with their evaluation, and associated clinical outcomes.
Varied reporting of incidental findings is problematic for clinicians who might be unable to determine whether the finding is new or just not previously reported. Conversely, for some findings, the radiologist will not have the information necessary to assess clinical relevance. Our community partners work closely with university program leaders to standardize LCS image specifications (e.g., slice thickness), making significant technical differences less likely. These results suggest that reporting discretion is the likely cause of the within-program variance of incidental findings, rather than differences between patients.
The strength of this study is the large “real-world” sample. Compared with the NLST, this sample has a higher proportion of current smokers and women. About 10% of the participants did not meet United States Preventive Services Task Force criteria, which is considered acceptable in a high-quality screening program (13). This study is limited by the absence of a radiologist’s adjudication of findings. The lower reporting rate for findings such as thyroid, liver, and kidney masses compared with rates reported in the literature suggests that the radiologists used discretion to determine what was clinically significant. For example, standards exist for reporting the extent of incidental lung disease/abnormalities (14), but these are not specified in Lung-RADS or in the context of LCS.
With the widespread implementation of LCS, strategies for consistently reporting and evaluating incidental findings are needed. Appropriate reporting and management of incidental findings on LCS have the potential to improve cost efficacy and health outcomes by facilitating the identification of clinically significant disease without an unnecessary investigation of clinically unimportant findings. It is important to assess the long-term outcomes of LCS incidental findings before we can make evidence-based decisions about the reporting and management of such findings.
Supplementary Material
Footnotes
Supported by National Institutes of Health (NIH) grant P30 CA77598 using the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota, and by the National Center for Advancing Translational Sciences, NIH (UL1TR000114). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Author disclosures are available with the text of this letter at www.atsjournals.org.
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